Additional laboratory and clinical studies are needed to further elucidate the interaction between tumor, tissue and system level factors
Additional laboratory and clinical studies are needed to further elucidate the interaction between tumor, tissue and system level factors. A potential limitation of this study was the limited sample size for certain subgroup comparisons. including BCL6, p53 and cMYC expression, but not EBV infection status, were significantly correlated with stromal immune infiltration, particularly FOXP3+ T cells. A higher density of infiltrating CD8+ T cell was significantly associated with reduced mortality in HIV-related DLBCL patients [odds ratio=0.30 (0.09C0.97) for 25% vs. 10%]. Conclusion These data provide evidence for the prognostic significance of cytotoxic T cells in determining outcomes of HIV-related lymphoma. hybridization of EBV encoded RNA and was considered positive if 75% of the DLBCL cells had detectable EBV. Among EBV-positive tumors, LMP1 expression was determined based on immunohistochemistry staining. Normal tonsillar lymphoid tissue was included as a positive control. Negative controls for each case consisted of substituting the primary antibody with isotype specific non-cross reacting antibody matching the primary antibody. The detailed information on TMA construction, antibody, incubation method and signal detection for each marker were described elsewhere. DLBCL Morphologic Variants DLBCL morphologic variant subtyping was performed by the two study pathologists (Said J and Zha H), who independently reviewed pathology reports, H&E slides and stained tumor marker expression data. Minor classification discrepancies on two patients were resolved by the pathologists after applying the World Health Organizations 2008 classification system of tumors of the hematopoietic and lymphoid tissues. Ascertainment of Patient Survival Two-year mortality was chosen as the outcome because most deaths in HIV-infected patients (85% in our study) occurred within two years after DLBCL diagnosis. Overall mortality ascertainment was complete for all subjects (even if the person terminated KP membership) through record linkage with KPs membership and utilization files, Californias state death file, and Social Security death records. As such, there was no loss-to-follow up. CAY10505 Covariates The International Prognostic Index (IPI) was calculated based on age, clinical stage, extranodal involvement, serum lactose dehydrogenase (LDH), and performance status[17, 18]. Age at DLBCL diagnosis, stage at diagnosis, extranodal involvement, and initial chemotherapy were collected from KPs cancer registries. Serum LDH level and circulating CD4 cell counts at DLBCL diagnosis (and CAY10505 their nadir) were obtained from the laboratory databases. Performance status and chemotherapy were ascertained from standardized medical record review. We collected HIV disease factors from HIV registries, including prior AIDS diagnosis, Rabbit polyclonal to ADI1 use of ART, and duration of known HIV infection. Statistical Analysis The density of the five stromal immune cells were calculated and compared by HIV status using the t-test statistic. Next, among HIV-infected patients, we compared the density of the stromal immune cells by stage at diagnosis, DLBCL variant (centroblastic, immunoblastic and plasmablastic), GC phenotype, prior AIDS diagnosis, ART use prior to DLBCL diagnosis, and tumor EBV infection and LMP1 status, using the Kruskal Wallis tests. The association between circulating CD4 cell count (both at DLBCL diagnosis and nadir) and infiltrating immune cells was examined using Pearsons correlation coefficient. Similarly, the association between infiltrating immune cells and tumor molecular characteristics, including the expression of BCL2, BCL6, p53, Ki-67 and cMYC, was examined using CAY10505 Pearsons correlation coefficient. Kaplan-Meier survival curves were generated for CD8+ and FOXP3+ T cells and CD68+ macrophage for the following density categories: 10%, 10C24%, 25C49%, 50C74%, and 75%. However, because less than 5 subjects had stromal immune cell density at 50% or greater, CAY10505 the following combined categories were presented: 10%, 10C24%, and 25%. Because most HIV-related.